Method for Carrying Out Chemical Reactions with the Aid of an Inductively Heated Heating Medium

ABSTRACT

The invention relates to a method for carrying out a chemical reaction for producing a target compound by heating in a reactor a reaction medium containing at least one first reactant, such that a chemical bond inside the first reactant or between the first and a second reactant is formed or modified. The reaction medium is brought into contact with a solid heating medium that can be warmed by electromagnetic induction and that is inside the reactor and is surrounded by the reaction medium. Said heating medium is heated by electromagnetic induction with the aid of an inductor and the target bond is formed from the first reactant or from the first and a second reactant and said target bond is separated from the heating medium.

This application is a continuation of International Application No.PCT/EP2008/063763 filed Oct. 14, 2008, which claims the benefit ofGerman Patent Application No. 10 2007 059 967.8 filed Dec. 11, 2007.

The present invention is in the field of chemical synthesis and relatesto a process for carrying out a chemical reaction with the help of aninductively heated heating medium.

In order to carry out thermally inducible chemical reactions, varioustechniques are known for heating the reactants. Heating by heatconduction is the most widely used. Here the reactants are present in areactor, wherein either the walls of the reactor are themselves heatedor wherein heat-transfer elements, such as for example heating coils orheat exchanger pipes or plates, are built into the reactor. This processis comparatively slow, so that firstly the reactants are heated slowlyand secondly the heat input cannot be rapidly suppressed or evencompensated for by cooling. An alternative to this consists in heatingthe reactants by irradiating microwaves into the reactants themselves orin a medium that contains the reactants. However, microwave generatorsrepresent a considerable safety risk as they are technically costly andthe danger exists for the leakage of radiation.

In contrast to this, the present invention provides a process, in whichthe reaction medium is heated by bringing it into contact with a heatingmedium that can be heated by electromagnetic induction and which isheated “from the exterior” by electromagnetic induction with the aid ofan inductor.

The process of inductive heating has been used for some time inindustry. The most frequent applications are melting, curing, sinteringand the heat treatment of alloys. However, processes such as gluing,shrinking or bonding of components are also known applications of thisheating technology.

Processes for the isolation and analysis of biomolecules are known fromthe German patent application DE 198 00 294, wherein the biomoleculesare bonded onto the surface of inductively heatable magnetic particles.This document states: “The principle of operation consists inadsorptively or covalently binding biomolecules to the surface of afunctional polymer matrix, in which the inductively heatable magneticcolloids or finely dispersed magnetic particles are encapsulated, saidbiomolecules being capable of binding analytes such as e.g. DNA/RNAsequences, antibodies, antigens, proteins, cells, bacteria, viruses orfungal spores according to the complementary affinity principle. Oncethe analytes have been bound to the matrix the magnetic particles can beheated in a high frequency magnetic alternating field to temperatures ofpreferably 40 to 120° C. that are relevant for analysis, diagnostics andtherapy.” Furthermore, this document treats the technical design ofrinsing systems and high frequency generators, which can be used in thisprocess. The cited document thus describes the use of inductivelyheatable particles for the analysis of complex biological systems orbiomolecules.

DE 10 2005 051637 describes a reactor system with a microstructuredreactor as well as a process for carrying out a chemical reaction insuch a reactor. Here the reactor as such is heated by electromagneticinduction. The heat transfer into the reaction medium results throughthe heated reactor walls. On the one hand, this limits the size of thesurface that is available for heating the reaction medium. On the otherhand, parts of the reactor that are not in direct contact with thereaction medium also need to be heated.

U.S. Pat. No. 5,110,996 describes the preparation of vinylidene fluorideby the gaseous phase reaction of dichlorodifluoromethane with methane ina heated reactor. The reactor was filled with a non-metallic filler. Ametallic hull that is heated from the exterior by electromagneticinduction surrounds the reaction chamber that contains this filler. Thereaction chamber itself is therefore heated from the exterior, wherebythe filler is likewise heated over time by radiating heat and/or thermalconductivity. A direct heating of the filler circulated by the reactantsdoes not occur if this filler is electrically conductive, as themetallic reactor wall shields the electromagnetic fields from theinduction coil.

WO 95/21126 discloses a gas phase process for preparing hydrogen cyanidefrom ammonia and a hydrocarbon with the aid of a metallic catalyst. Thecatalyst is inside the reaction chamber so that reactants circulateround the catalyst. It is heated from the exterior by electromagneticinduction with a frequency of 0.5 to 30 MHz, i.e. with a high frequencyalternating field. In regard to this, this document cites the previouslycited document U.S. Pat. No. 5,110,996 with the remark that normally,inductive heating is carried out in the frequency range from about 0.1to 0.2 MHz. However, this indication is not comprised in the cited U.S.Pat. No. 5,110,996, and it is unclear what it refers to.

WO 00/38831 is concerned with controlled adsorption and desorptionprocesses, wherein the temperature of the adsorber material iscontrolled by electromagnetic induction.

The subject matter of the present invention is a process for carryingout a chemical reaction for producing a target compound by heating areaction medium comprising at least one first reactant in a reactor,whereby a chemical bond within the first reactant or between the firstand a second reactant is formed or modified, wherein the reaction mediumis brought into contact with a solid heating medium that can be heatedby electromagnetic induction and that is inside the reactor and issurrounded by the reaction medium, and said heating medium is heated byelectromagnetic induction with the aid of an inductor, wherein thetarget compound is formed from the first reactant or from the first anda second reactant and wherein said target compound is separated from theheating medium.

Accordingly, the chemical reaction takes place by heating a reactionmedium that comprises at least one first reactant. This includes thepossibility that the reaction medium, for example a liquid, is itselfinvolved in the reaction and therefore represents a reactant. The wholeof the reaction medium can therefore consist of one reactant. Further, areactant can be dissolved or dispersed in the reaction medium, whereinthe reaction medium can itself be inert or can represent for its part areactant. Or one, two or more reactants are dissolved or dispersed in areaction medium that is itself not changed by the chemical reaction.

In this regard the reaction medium can consist of a single reactant orcomprise it, wherein reactant molecules react with one another orwherein a modification of the chemical bonding system can occur in theindividual molecules of the reactant itself. The reactant is chemicallymodified in both cases. In the general case, however, two or morereactants participate with one another in reaction, wherein chemicalbonds within and/or between the individual reactants are rearranged orformed.

The solid heating medium is surrounded by the reaction medium. This canmean that the solid heating medium, apart from possible peripheralzones, is present within the reaction medium, e.g. when the heatingmedium is present in the form of particles, filings, wires, gauze, wool,packing materials etc. However, this can also mean that the reactionmedium flows through the heating medium through a plurality of cavitiesin the heating medium, when for example the latter consists of one ormore membranes, a bundle of pipes, a rolled up metal foil, frits, porouspacking materials or from a foam. In this case the heating medium isalso essentially surrounded by the reaction medium, as the majority ofits surface (90% or more) remains in contact with the reaction medium.In contrast to this is a reactor, whose external wall is heated byelectromagnetic induction (such as for example that cited in thedocument U.S. Pat. No. 5,110,996), where only the inner reactor surfacecomes into contact with the reaction medium.

The wall of the reactor is made of a material that neither shields norabsorbs the electromagnetic alternating field produced by the inductorand therefore is itself not heated up. Consequently, metals areunsuitable. For example it can consist of plastic, glass or ceramics(such as for example silicon carbide or silicon nitride). The lastmentioned is particularly suitable for reactions at high temperatures(500-600° C.) and/or under pressure.

The above-described method has the advantage that the thermal energy forcarrying out the chemical reaction is not brought into the reactionmedium through surfaces such as for example the reactor walls, heatingcoils, heat exchange plates or the like, but rather is produced directlyin the volume of the reactor. The ratio of heated surface to volume ofthe reaction medium can, in this case, be considerably greater than fora heating through heat transfer surfaces, as is also the case, forexample, cited in DE 10 2005 051637 in the introduction. In addition tothis, the degree of efficiency of electrical current to thermal outputis improved. By switching on the inductor, the heat can be generated inthe totality of the solid heating medium, which remains in contactthrough a very high surface with the reaction medium. Switching off theinductor very quickly suppresses any further thermal input. This permitsa very targeted reaction control.

After the target compound is formed it is separated from the heatingmedium. In the best case the target compound is isolated in pure form,i.e. free of solvent and with no more than the usual impurities.However, the target compound can also be separated from the heatingmedium in a mixture with reactants or as a solution in the reactionmixture and then be isolated by further working up or be transferredinto another solvent, as is desired. The process is therefore suitablefor the preparative manufacture of the target compound in order to beable to use these in a further step.

In contrast to this are processes, in which a chemical reaction isindeed likewise initiated by electromagnetic induction of a heatingmedium, but the reaction does not serve to prepare a target compoundthat is separated from the heating medium after the end of the reaction.An example of this is the curing of resin systems, wherein the curingreaction is initiated on particles that are dispersed in the resinsystem and which are heated by electromagnetic induction. In such a casethe particles remain in the cured resin system and no defined targetcompound is isolated. The same is true for the opposite case, in whichan adhesive compound is unglued again by the inductively heatedparticles that are present in the adhesive matrix. A chemical reactioncan indeed occur in this case, but no target compound is isolated.

The heating medium consists of an electrically conductive material thatis heated by the action of an alternating electrical field. It ispreferably selected from materials that possess a very high surface tovolume ratio. For example the heating medium can be selected in eachcase from electrically conductive filings, wires, meshes, wool,membranes, porous frits, pipe bundles (of three or more pipes), rolledup metal foils, foams, packing materials such as for example granules orpellets, Raschig rings and particularly particles that preferably havean average diameter of not more than 1 mm. For example, mixed metallicelements can be employed as the heating medium, as are used for staticmixers. In order to be heatable by electromagnetic induction, theheating medium is electrically conductive, for example metallic (whereinit can be diamagnetic) or it exhibits enhanced interaction towardsdiamagnetism with a magnetic field and in particular is ferromagnetic,ferrimagnetic, paramagnetic or superparamagnetic. In this regard it isimmaterial whether the heating medium is of an organic or inorganicnature or whether it contains both inorganic as well as organiccomponents.

In a preferred embodiment, the heating medium is selected from particlesof electrically conductive and/or magnetizable solids, wherein the meanparticle size of the particles is from 1 to 1000, especially from 10 to500 nm. The mean particle size and when necessary also the particle sizedistribution can be determined for example by light scattering. Magneticparticles are preferably selected, for example ferromagnetic orsuperparamagnetic particles, which exhibit the lowest possible remanenceor residual magnetism. This has the advantage that the particles do notadhere to each other. The magnetic particles can be in the form of“ferrofluids”, i.e. liquids, in which nanoscale ferromagnetic particlesare dispersed. The liquid phase of the ferrofluid can then serve as thereaction medium.

Magnetizable particles, in particular ferromagnetic particles, whichexhibit the desired properties, are known from the prior art and arecommercially available. The commercially available ferrofluids may becited. Examples for the manufacture of magnetic nano-particles, whichcan be used in the context of the inventive process, can be found in thearticle by Lu, Salabas and Schüth: “Magnetische nano-Partikel: Synthese,Stabilisierung, Funktionalisierung and Anwendung”, Angew. Chem. 2007,119, pp. 1242 to 1266.

Suitable nano-particles with different compositions and phases areknown. The following examples may be cited: pure metals such as Fe, Coand Ni, oxides such as Fe₃O₄ and gamma-Fe₂O₃, spinel type ferromagnetssuch as MgFe₂O₄, MnFe₂O₄ and CoFe₂O₄ as well as alloys such as CoPt₃ andFePt. The magnetic nano-particles can be of a homogeneous structure orcan possess a core-shell structure. In the latter case the core andshell can consist of different ferromagnetic or even antiferromagneticmaterials. However, embodiments are also possible, in which amagnetizable core that can be for example ferromagnetic,antiferromagnetic, paramagnetic or superparamagnetic, is surrounded by anon-magnetic material. An organic polymer for example, can representthis material. Or the shell consists of an inorganic material such asfor example silica or SiO₂. A coating of this type can prevent achemical interaction between the reaction medium or the reactants withthe material of the magnetic particle itself. In addition, the shellmaterial can be surface modified, without the material of themagnetizable core interacting with the functionalizing entity. In thisregard, a plurality of particles of the core material can be enclosedtogether into a shell of this type.

Nano-scale particles of superparamagnetic substances for example can beemployed as the heating medium and are selected from aluminum, cobalt,iron, nickel or their alloys, metal oxides of the type n-maghemite(gamma-Fe₂O₃), n-magnetite (Fe₃O₄) or ferrites of the type MeFe₂O₄,wherein Me is a divalent metal selected from manganese, copper, zinc,cobalt, nickel, magnesium, calcium or cadmium. Preferably the meanparticle size of these particles is <100 nm, preferably ≦=51 nm andparticularly preferably <30 nm.

An exemplary suitable material is available from Evonik (formallyDegussa) under the name MagSilica®. In this material, iron oxideparticles having a size between 5 and 30 nm are embedded in an amorphoussilica matrix. Such iron oxide-silicon dioxide composite particles,which are described in more detail in the German patent application DE101 40 089, are particularly suitable.

These particles can comprise superparamagnetic iron oxide domains with adiameter of 3 to 20 nm. This is understood to mean superparamagneticregions that are spatially separated from one another. The iron oxidecan be present in these domains in a single modification or in variousmodifications. A particularly preferred superparamagnetic iron oxidedomain is gamma-Fe₂O₃, Fe₃O₄ and mixtures thereof.

The content of the superparamagnetic iron oxide domains of theseparticles can be between 1 and 99.6 wt. %. The individual domains areseparated from one another and/or surrounded by a non-magnetizablesilicon dioxide matrix. The region containing a content of thesuperparamagnetic iron oxide domains is preferably >30 wt. %,particularly preferably >50 wt. %. The achievable magnetic effect of theinventive particle also increases with the content of thesuperparamagnetic regions. The silicon dioxide matrix also stabilizesthe oxidation level of the domain in addition to separating the spatialseparation of the superparamagnetic iron oxide domains. Thus, forexample, magnetite is stabilized as the superparamagnetic iron oxidephase by a silicon dioxide matrix. These and further properties of theseparticles that are particularly suitable for the present invention arelisted in more detail in DE 101 40 089 and in WO 03/042315.

Furthermore, nano-scale ferrites such as those known for example from WO03/054102 can be employed as the heating medium. These ferrites possessthe composition (M^(a) _(1-x-y)M^(b) _(x)Fe^(II) _(y))Fe^(III) ₂O₄, inwhich

M^(a) is selected from Mn, Co, Ni, Mg, Ca, Cu, Zn, Y and V,M^(b) is selected from Zn and Cd,x stands for 0.05 to 0.95, preferably 0.01 to 0.8,y stands for 0 to 0.95 andthe sum of x and y is maximum 1.

The particles that can be heated by electromagnetic induction canrepresent the heating medium without any additional additives. However,it is also possible to mix the particles that can be heated byelectromagnetic induction with other particles that cannot be heated byelectromagnetic induction. Sand for example can be used. Accordingly,the inductively heatable particles can be diluted with non-inductivelyheatable particles. This allows an improved temperature control. Inanother embodiment, the inductively heatable particles can be admixedwith non-inductively heatable particles that have catalytic propertiesfor the chemical reaction to be carried out or that participate in otherways in the chemical reaction. These particles are then not directlyheated by electromagnetic induction, but rather indirectly, in that theyare heated by contact with the heatable particles or by heat transferfrom the reaction medium.

If nano-scale electromagnetically inductively heatable particles areblended with coarser non-inductively heatable particles, then this canlead to a decreased packing density of the heating medium. Inembodiments, in which the reaction medium flows through a packing madeof the heating medium, this can result in a desired reduction of thepressure drop in the flow-through reactor.

The solid heating medium can be surface-coated with a substance that iscatalytically active for the desired chemical reaction. For examplethese can be organic molecules or biomolecules having an enzymaticaction. In this case care should be taken to ensure that the heatingmedium is not heated too strongly to cause these molecules to lose theirenzymatic action.

In particular, the inductively heatable heating medium can be coatedwith metal atoms or metallic compounds, whose catalytic activity isknown. For example, atoms or compounds of metals can be of thelanthanide series, especially Sm or Ce, Fe, Co, Ni or precious metals,preferably platinum metals and especially Pt or Pd.

Particles that comprise magnetizable domains in a silicon dioxide matrixor silica matrix, for example the composite particles of iron oxide andsilicon dioxide that are described above, are particularly suitable forcoating with catalytically active atoms or compounds. The silicondioxide shell carries, as is described in more detail in WO 03/042315,reactive OH groups, whose reactivity can be exploited in order to fixthe catalytically active substance to the particle surface. Someexamples of this are presented in the experimental part.

In principle the chemical reaction can be carried out in a continuous orbatch manner. If the reaction is carried out in a batch mode, then thereactive medium and the inductively heated solid heating mediumpreferably move relative to one another during the reaction. When usinga particulate heating medium this can be effected in particular bystirring the reaction mixture with the heating medium or by swirling theheating medium in the reaction medium. If for example meshes or wool areused in a filiform shaped heating medium, then the reaction vessel thatcontains the reaction medium and the heating medium can be shaken.

A preferred embodiment of a batch mode reaction consists in the reactionmedium being present together with particles of the heating medium in areaction vessel, and is moved with the help of a moving element locatedin the reaction medium, wherein the moving element is arranged as theinductor, by which the particles of the heating medium are heated byelectromagnetic induction. Consequently, in this embodiment the inductoris found inside the reaction medium. The moving element can be designedfor example as a stirrer or as a plunger that moves back and forth.

Provision for externally cooling the reactor during the chemicalreaction can also be made. This is possible in particular for batchmodes if, as described above, the inductor is immersed in the reactionmedium. The supply of the electromagnetic alternating field into thereactor is then not impeded by the cooling apparatus.

The reactor can be cooled from inside by cooling coils or heatexchangers or preferably from outside. Optionally precooled water oreven a coolant for example whose temperature is below 0° C. can be usedfor cooling. Exemplary coolants of this type are ice-table saltmixtures, methanol/dry ice or liquid nitrogen. The cooling creates atemperature gradient between the reactor wall and the inductively heatedheating medium. This is particularly pronounced when a coolant with atemperature significantly below 0° C. is used, for example methanol/dryice or liquid nitrogen. The reaction medium that is heated by theinductively heated heating medium is then externally cooled down again.In this case the chemical reaction of the reactants then only occurswhen it is in contact with the heating medium or is at least in itsdirect proximity. Due to the relative movement of the reaction medium tothe heating medium, products formed during the reaction rapidly reachcooler regions of the reaction medium, such that their thermalsubsequent reaction is inhibited. In this way, a desired reaction pathcan be kinetically selected when a plurality of possible reaction pathsof the reactant(s) exist.

In an alternative embodiment, the chemical reaction is carried outcontinuously in a flow-through reactor that is at least partially filledwith the solid heating medium and thereby possesses at least one heatingzone that can be heated by electromagnetic induction, wherein thereaction medium flows continuously through the flow-through reactor andwherein the inductor is located outside the reactor. Here the reactionmedium flows round the heating medium, e.g. when this is in the form ofparticles, filings, wires, meshes, wool, packing materials etc. Or thereaction medium flows through the heating medium through a plurality ofcavities in the heating medium, when this consists for example of one ora plurality of membranes, fits, porous packing materials or a foam.

The flow-through reactor is preferably designed as a tubular reactor. Inthis case the inductor can totally or at least partially surround thereactor. The electromagnetic alternating field generated by the inductoris then fed from all sides or at least from a plurality of places intothe reactor.

“Continuously” is hereby understood to mean as usual a reaction mode, inwhich the reaction medium flows through the reactor in at least such aperiod of time that a total volume of reaction medium that is large incomparison with the internal volume of the reactor itself has flowedthrough the reactor, before the flow of reaction medium is discontinued.“Large” in this context means: “at least twice as large”. Naturally, acontinuously operated reaction of this type also has a beginning and anend.

In this continuous process in a flow-through reactor it is possible forthe reactor to have a plurality of heating zones. The different heatingzones can be differently heated for example. This can be the result ofarranging different heating media in the flow-through reactor or due todifferently mounted inductors along the reactor.

The use of at least two heating zones constitutes a particularembodiment, in that the flow-through reactor possesses a first and asecond heating zone, wherein the first heating zone in the flowdirection of the reaction medium does not comprise a heating mediumloaded with a catalytically active substance, whereas the second heatingzone in the flow direction of the reaction medium does comprise aheating medium loaded with a catalytically active substance. In analternative embodiment, the opposite arrangement is chosen for thecatalytically and non-catalytically active heating medium. This allowsan additional non-catalytically initiated reaction step to be carriedout prior to or after a catalytically active reaction step.

The solvent or the reaction medium can also be initially preheated in aconventional manner prior to its contacting the heating medium in thereaction.

When required, a cooling zone, for example in the form of a coolingjacket around the reactor, can be provided after the (last) heatingzone.

Furthermore, after leaving the heating zones the reaction medium can bebrought into contact with an absorbing substance that removesby-products or impurities from the reaction medium. For example it canbe a molecular sieve, through which flows the reaction medium afterhaving left the heating zones. In this way the product can be purifiedimmediately after its production.

Depending on the chemical reaction rate, the product yield canoptionally be increased by at least partially recycling the reactionmedium that has flowed through the solid heating medium back through thesolid heating medium again. In this way the impurities, by-products oreven the desired major product can be removed from the reaction mediumafter each passage through the solid heating medium. The various knownseparation methods are suitable for this, for example absorption on anabsorbing substance, separation through a membrane process,precipitation by cooling or separation by distillation. This ultimatelyenables a complete conversion of the reactant(s) to be achieved. This isalso true in cases where without separating the reaction product thechemical reaction only proceeds to an equilibrium state.

The required total contact time of the reaction medium with theinductively heated heating medium needs to be chosen as a function ofthe kinetics of each chemical reaction. The slower the desired chemicalreaction, the longer the contact time. This has to be empiricallyadjusted for each individual case. As a guide, the reaction mediumpreferably flows once or a plurality of times through the flow-thoughreactor with a speed such that the total contact time of the reactionmedium with the inductively heated heating medium is in the range of onesecond to 2 hours prior to separating the target product. Shortercontact times are conceivable but more difficult to control. Longercontact times can be required for particularly slow chemical reactions,but increasingly worsen the economics of the process.

Independently of whether the reaction is run batch wise or continuouslyin a flow-through reactor, the reactor can be designed as a pressurereactor and the chemical reaction is carried out at a pressure greaterthan atmospheric pressure, preferably under at least 1.5 bar. It is wellknown that the product yield can be increased in this way when theproduct formation (formation of the target compound) is associated witha volume reduction. For two or more possible reactions, the formation ofthat particular product can be preferred that results in the greatestreduction in volume.

The inventive process is preferably carried out in such a way that thereaction medium in the reactor is in liquid form under the set reactionconditions (particularly temperature and pressure). This generally makespossible, based on the reactor volume, better volume/yields over timethan for gas phase reactions.

The nature of the heating medium and the design of the inductor arematched to each other in such a way to permit the reaction medium to beheated up. A critical variable for this is firstly the rated power ofthe inductor in watts as well as the frequency of the alternating fieldgenerated by the inductor. In principle, the greater the mass of theheating medium to be inductively heated, the higher will be the chosenpower. In practice, the achievable power is limited primarily by theability to cool the generator required for supplying the inductor.

Particularly suitable inductors generate an alternating field with afrequency in the range of about 1 to about 100 kHz, preferably from 10to 80 kHz and particularly preferably from about 10 to about 30 kHz.Inductors of this type together with the associated generators arecommercially available, for example from IFF GmbH in Ismaning (Germany).

Thus the inductive heating is preferably carried out with an alternatingfield in the medium frequency range. This has the advantage, whencompared with an excitation with higher frequencies, for example withthose in the high frequency range (frequencies above 0.5, especiallyabove 1 MHz), that the energy input into the heating medium can bebetter controlled. This is particularly true when the reaction medium isin liquid form under the reaction conditions. Consequently, in thecontext of the present invention the reaction medium is preferably inliquid form and inductors are employed that generate an alternatingfield in the abovementioned medium frequency range. This permits aneconomic and well controllable reaction process.

In a special embodiment of the inventive process, the heating medium isferromagnetic and exhibits a Curie temperature in the range of about 40°C. to about 250° C., and is selected such that the Curie temperaturedoes not differ by more than 20° C., preferably by not more than 10° C.from the selected reaction temperature. This affords an inherentprotection against an unintended overheating. The heating medium can beheated by electromagnetic induction only up to its Curie temperature; itwill not be heated any further above this temperature by theelectromagnetic alternating field. Even with a malfunction of theinductor, the temperature of the reaction medium is prevented from anyunintentional increase to a value significantly above the Curietemperature of the heating medium. Should the temperature of the heatingmedium fall below its Curie temperature then it will again be heated byelectromagnetic induction. This leads to a self-regulation of thetemperature of the heating medium in the region of the Curietemperature.

The inventive process is particularly suitable for carrying outthermally induced reactions. In principle there is no limit to thepossible reaction types—with the proviso that neither reactionconditions (such as for example pH) nor educts are chosen that coulddestroy the heating medium. For example, chemical reactions can becarried out in which at least one chemical bond between two carbon atomsor between a carbon atom and an atom X is formed, cleaved or rearranged,wherein X is selected from: H, B, O, N, S, P, Si, Ge, Sn, Pb, As, Sb, Biand halogens. The reaction can also involve a rearrangement of chemicalbonds, such as occurs for example in cycloadditions and Diels-Alderreactions. For example, the thermally induced reaction can correspond toat least one of the following reaction types: oxidation, reduction(including hydrogenation), fragmentation, addition to a double or triplebond (incl. cycloaddition and Diels-Alder reactions), substitution (SN₁or SN₂, radical), especially aromatic substitution, elimination,rearrangement, cross coupling, metathetical reactions, formation ofheterocycles, ether formation, ester formation or transesterification,amine or amide formation, urethane formation, pericyclic reactions,Michael addition, condensation, polymerization (radical, anionic,cationic), polymer grafting.

For reduction or hydrogenation reactions, suitable reducing agents orhydrogen sources are for example: cycloalkenes such as cyclohexene,alcohols such as ethanol, inorganic hydrogenation reagents such assodium borohydride or sodium aluminum hydride.

Fats or oils for example can be fragmented. This can occur in solution,but also in the substance in the absence of solvent. In the latter casethe fat or oil as such represents the whole reaction medium.

Reactions, which lead to inorganic target products, are also possible ofcourse.

The following examples exemplify chemical reactions on a laboratoryscale that were carried out with the inventive process in a flow-throughreactor. The present invention is of course not limited to these.

EXAMPLES

The invention was tested on a laboratory scale. Glass tubes (10 cm long)and of varying inner and outer diameters were used as the tubularreactors. The tubes were provided with screw connections on both ends soas to be able to attach the HPLC and suitable tubing.

The inductor that was used had the following performancecharacteristics: inductivity: 134 μHenry, winding count for the spool:=2-16, cross sectional area=2.8 mm2 (the cross sectional area resultsfrom the number of the conductor wires in the inductor and theirdiameter.) The diameter of the gap for receiving the tubular reactor was12 mm. For all experiments the inductor was operated with a frequency of25 kHz.

In the experiments the specified frequency of 25 kHz was left constantand the heating control was undertaken solely through the PWM(PWM=on/off switch for a square wave signal at a fixed fundamentalfrequency). In the following the PWM is stated in ‰. The inducedtemperature was measured with a thermocouple and an infraredthermometer. The thermocouple was mounted directly behind the reactor inthe fluid so as to permit an accurate as possible measurement. However,due to the metallic components of the thermocouple, a minimum distanceof 4 cm had to be observed. A laser infrared thermometer with closefocus optics was used for the second temperature measurement. Themeasurement point had a diameter of 1 mm. With this method the surfacetemperature of the reactor should be measured in order to obtain asecond measurement point for the temperature determination. The emissionfactor of the material is an important constant for an infraredmeasurement. It is a measure of the heat emission. An emission factor of0.85 was used and corresponds to that of an average glass.

Heating Tests with Different Heating Media:

The experiments were carried out at a frequency of 25 kHz with an EW5unit (power 5 watts) with dry powders (no flow). Each heating timelasted for 10 minutes and the temperature was measured with a pyrometer.The following heating media were tested:

a) MagSilica® 58/85 from Evonik (formerly Degussa),

b) Manganese ferrite powder from SusTech GmbH, Darmstadt,

c) Bayferrox® 318 M: synthetic alpha-Fe₃O₄ from Harald Scholz & Co.GmbH,

d) Manganese-zinc-ferrite, surface coated with oleic acid, ferritecontent 51.7 wt. %, SusTech GmbH, Darmstadt

After 10 minutes the following temperatures were reached:

Sample PWM = 300‰ PWM = 400‰ a) 170° C. 220° C. b) 130° C. 150° C. c) 70° C. 150° C. d)  60° C.  65° C.Reactions Carried Out with Different Heating Media:

In each case the reactor was filled with 3.3 g of the cited material inorder to obtain the desired heating by the inductor for the reactions.

Manganese Ferrite (b):

Bayferrox (c):

In addition, the heating of rolled copper foil by electromagneticinduction was examined: The foil was heated at a frequency of 20 kHz anda PWM of only 175‰ after less than 10 minutes to >160° C.

The heating medium for the following experiments was Magsilica 58/85from Evonik (formerly Degussa) and was optionally surface modifiedaccording to the following process. The icon

represents MagSilica, and the icon

represents a MagSilica residue after reaction, in the following reactionschemes.

Surface Modification of the Heating Medium with Catalysts:

Shakers were used for preparing the catalysts so as to ensure a thoroughmixing of the substrates. Conventional filter papers proved to beunsuitable for washing as the pores blocked up too quickly. Consequentlythe solids were centrifuged at each washing step. The magneticproperties or the magnetic separation were tested with a commerciallyavailable magnet.

Preparation of Catalyst 7:

1. Step: Catalyst Precursor 14

MagSilica 50/85® (15.0 g) was heated under reflux for 2 h in bidistilledH2O (150 mL) and then dried under high vacuum. The solid was suspendedin toluene (180 mL) and shaken with(p-chloromethyl)phenyltrimethoxysilane (15 mL, 68.1 mmol) for 26 h. Thereaction mixture was heated under reflux for 3 h. After cooling thesolid was centrifuged and washed with toluene (2×40 mL). After dryingunder high vacuum 12.1 g of 14 were obtained as a black, magneticpowder.

2. Step: Catalyst Precursor 61

14 (12.0 g) was suspended in a toluene solution (350 mL) saturated withtrimethylamine and shaken for 72 h. The solid was centrifuged and washedwith toluene (3×40 mL) and dried under high vacuum. 12.4 g of 61 wereobtained as a black, magnetic powder.

3. Step: Catalyst Precursor 15

61 (3.0 g) was suspended in bidistilled H2O (150 mL) and shaken with asolution of sodium tetrachloropalladate (100 mg, 0.34 mmol) inbidistilled H2O (10 mL) for 18 h. The solid was centrifuged and washedwith bidistilled H2O (2×40 mL) and dried under high vacuum. 2.7 g of 15were obtained as a black, magnetic powder.

4. Step: Catalyst Precursor 7

15 (2.7 g) was suspended in bidistilled H2O (30 mL) and treated with asolution of sodium borohydride (0.64 g, 16.9 mmol) in bidistilled H2O(15 mL). The reaction mixture was shaken for 5 h, centrifuged and washedwith bidistilled H2O, sat. NaCl solution and H2O (40 mL each) and driedunder high vacuum. 2.6 g of 7 were obtained as a black, magnetic powder.The catalyst loading was 6.7×10−5 mmol Pd/mg catalyst (ICP-MS traceanalysis).

Preparation of Catalyst 6:

1. Step: Catalyst Precursor 12

MagSilica 50/85® (6.0 g) was dried at 200° C. for 6 h under high vacuumand then suspended in abs. toluene (150 mL) in an inert gas atmosphere.3-Aminopropyltrimethoxysilane (4.5 mL, 25.3 mmol) in abs. toluene (10mL) was added. The reaction mixture was shaken for 16 h and centrifuged.The solid was washed with abs. toluene (2×40 mL) and aqueous toluene(1×40 mL) and then dried under high vacuum. 5.3 g of 12 were obtained asa black, magnetic powder.

2. Step: Catalyst Precursor 62

In an inert gas atmosphere 12 (4.0 g) was suspended in abs. diethylether (180 mL) and treated with HBF4 OEt2 (10 mL, 38.9 mmol). Thereaction mixture was shaken for 2 h. The solid was then centrifuged andwashed with diethyl ether, aqueous diethyl ether, sat. NaCl solution andbidistilled H2O (40 mL of each) and dried under high vacuum. 3.5 g of 62were obtained as a black, magnetic powder.

3. Step: Catalyst Precursor 13

62 (3.0 g) was suspended in bidistilled H2O (150 mL) and treated withsodium tetrachloropalladate (0.5 g, 1.7 mmol) in bidistilled H2O (10mL). The reaction mixture was shaken for 12 h. The solid was washed withbidistilled H2O until the solution was only weakly yellowish (3×40 mL)and then dried under high vacuum. 2.8 g of 13 were obtained as a black,magnetic powder. The catalyst loading was 3.7×10−5 mmol Pd/mg catalyst(ICP-MS trace analysis).

4. Step: Catalyst Precursor 6

13 (2.5 g) was suspended in bidistilled H2O (40 mL) and treated with asolution of sodium borohydride (0.64 g, 16.9 mmol) in bidistilled H2O(15 mL). The reaction mixture was shaken until the evolution of gasceased. The solid was washed with bidistilled H2O, saturated NaClsolution and bidistilled H2O (40 mL each) and dried under high vacuum.2.3 g of 6 were obtained as a black, magnetic powder. The catalystloading was 3.7×10−5 mmol Pd/mg catalyst.

Catalyst 8

MagSilica 50/85® (2.0 g) was suspended in EtOH and stirred with asolution of palladium nitrate dihydrate (84 mg, 0.32 mmol) in EtOH (10mL) at 50° C. for 30 min. The reaction mixture was concentrated undervacuum until dry. After drying under vacuum, 1.92 g of 8 were obtainedas a black, magnetic powder. The catalyst loading was 11.3×10−5 mmolPd/mg catalyst.

Preparation of Catalyst 9:

1. Step: Catalyst Precursor 63

MagSilica 50/85® (3.0 g) was heated under reflux for 2 h in bidistilledH2O (50 mL) and then dried under high vacuum. The black solid indodecane (18 mL) was treated with DVB (0.41 g, 5.3 m %), VBC (7.11 g,94.7 m %) and AIBN (37.5 mg, 0.5 m %) and stirred with a KPG-stirrer at70° C. for 16 h. The resulting black suspension was purified in asoxhlet extraction unit for 13 h with chloroform. The product wasseparated from the residual polymer and dried under high vacuum. 4.4 gof 63 were obtained as a black-greenish, magnetic powder.

2. Step: Catalyst Precursor 64

63 (4.4 g) was suspended in a toluene solution (350 mL) saturated withtrimethylamine and shaken for 93 h. The solid was centrifuged and washedwith toluene (3×40 mL). After drying under high vacuum a black-greenish,magnetic powder was obtained. 4.1 g of 63 were obtained.

3. Step: Catalyst Precursor 65

64 (4.1 g) was suspended in bidistilled H2O (150 mL) and shaken with asolution of sodium tetrachloropalladate (700 mg, 2.38 mmol) inbidistilled H2O (10 mL) for 17 h. The solid was centrifuged, washed withbidistilled H2O (3×40 mL) and dried under high vacuum. A black-greenish,magnetic solid was obtained. The crude product was employed withoutdrying in the following reaction.

4. Step: Catalyst 9

65 (4.0 g) was suspended in bidistilled H2O (50 mL) and treated with asolution of sodium borohydride (0.5 g, 13.2 mmol) in bidistilled H2O (15mL). The reaction mixture was shaken for 2 h, centrifuged, washed withbidistilled H2O, sat. NaCl solution and H2O (40 mL each) and dried underhigh vacuum. 3.3 g of 9 were obtained as a black-greenish, magneticpowder.

Several chemical reactions that were carried out with the inventiveprocess are shown below. Dimethylformamide (DMF) was used as the solventin all cases. As a comparison, the same reactions were also carried outwith conventional heating in a heated bath with the same temperaturesand reaction times. The comparative reaction yields are presented in thetables, wherein “thermal” means the conversion in the heating bath(comparison) and “inductive” means the conversion after the inventiveprocess. In the inventive process the total reaction time was attainedin that the reaction medium was circulated and accordingly flowedfrequently through the reactor.

In order to achieve approximately the same reaction temperature in theinventive process as in the thermal process, preliminary experiments forthe heating behavior were carried out. For this, DMF was passed througha mixture of MagSilica® and sand (ca. 67 vol. % MagSilica® and 33 vol. %sand) in the tubular reactor. The inductor was always operated at 25kHz. These conditions were also adhered to for the individual reactions.

Results of the Heating Tests:

TABLE 1 Heating Table. Measurement time External temp. Fluid temp. PWM[‰] [min] [° C.]^(a) [^(°)C.] 600 2 >170 —^(c) 400 4 >170 —^(c) 35010 >170 72 325 15 145 60 300 15 136 49 250 15 71 37 225 15 54 20 200 1533 19 Measurement up to each constant temperature with 25 kHz, 2 mL/minin DMF ,^(a)measured with thermocouple, ^(b)measured with infraredthermometer, ^(c)not measured due to liquid evaporation.

Examples of Reactions:

TABLE 2 Heck-Mizoroki Coupling, 1 mmol aryl halide, 3 eq. Styrene, 3n-B₃N, 2.8 mol % catalyst 7, reaction time 1 h each, flow rate 2 mL/min,PWM = 325%.

Ex. Conversion Conversion no. Aryl halide Alkene Product thermal [%]inductive [%] 1

0 7.5 2

60.0 84.2

TABLE 3 Additional catalysts; Suzuki-Miyaura Reaction 2 mL/min, reactiontime each 1 h,: 0.5 mmol Aryl halide, 1.5 eq. boronic acid, 2.4 eq. CsF,PWM 750 % Suzuki-Miyaura Reaction:

Conversion Conversion Catalyst Ex. no. thermal [%] inductive [%]

3 23.0 49.1 5% Pd/Aktivkohle^(a) 4 5.8 58.8

5 50.2 78.7

6 — 97.4 ^(a)1 mol%, ^(b)2.8 mol%,.

Example 7

Transesterification of ethyl cinnamate 59 to methyl cinnamate 60. Thisexperiment was carried out following method of the literature (K.Jansson, T. Fristedt, A. Olsson, B. Svensson, S. Jönsson, J. Org. Chem.,2006, 71, 1658-1667). An excess of sodium methanolate was used in orderto shift the transesterification equilibrium to the desired product.With inductive heating (flow rate: 2 mL/min, PWM=240‰) 93% product wasisolated after 25 min.

Additional flow-through thermal reactions with inductive heating

(prom=PWM in ‰. The numbers in % below the product formula state theproduct yield.)

Example 8 Syntheses of Heterocycles

Example 9 Hartwig-Buchwald Coupling

Example 10 Claissen Rearrangement

Example 11 Decarboxylation

(PH 343-48 states the batch number of the MagSilica®.)

Example 12 Hydrogenation

Example 13 Reduction

In examples 12 and 13 the Pd/C catalyst (palladium on active carbon) wasemployed in a mixture with MagSilica®. Cyclohexene essentially served asthe reducing agent (hydrogen source).

Example 14 Rearrangement with C—C Bond Formation

1. A process for carrying out a chemical reaction for producing a targetcompound by heating a reaction medium comprising at least one firstreactant in a reactor, whereby a chemical bond within the first reactantor between the first and a second reactant is formed or modified,wherein the reaction medium is brought into contact with a solid heatingmedium that can be heated by electromagnetic induction and that isinside the reactor and is surrounded by the reaction medium, and saidheating medium is heated by electromagnetic induction with the aid of aninductor, wherein the target compound is formed from the first reactantor from the first and a second reactant and wherein said target compoundis separated from the heating medium, wherein the reaction medium in thereactor is present as a liquid and the inductor generates an alternatingfield with a frequency in the range of 1 to 100 kHz.
 2. The processaccording to claim 1, wherein the heating medium is selected fromparticles of electrically conductive and/or magnetizable solids, whereinthe mean particle size of the particles is between 1 and 1000 nm.
 3. Theprocess according to claim 2, wherein the heating medium is selectedfrom particles of magnetizable solids, wherein each particle comprisesat least one core of a magnetizable material that is encapsulated by anon-magnetic material.
 4. The process according to claim 1, wherein theheating medium is selected from particles of magnetizable solids, andwherein these are present in a mixture with additional particles thatare not able to be heated by electromagnetic induction.
 5. The processaccording to claim 3, wherein the heating medium is selected fromparticles of magnetizable solids, and wherein these are present in amixture with additional particles that are not able to be heated byelectromagnetic induction
 6. The process according to claim I, whereinthe solid heating medium is surface coated with a substance that iscatalytically active for the chemical reaction.
 7. The process accordingto claim 1, wherein the chemical reaction is carried out batch-wise,wherein the reaction medium and the solid heating medium move relativeto each other during the reaction.
 8. The process according to claim 7,wherein the reaction medium is present together with particles of theheating medium in a reaction vessel, and is moved with the help of amoving element located in the reaction medium, wherein the movingelement is arranged as an inductor, by which the particles of theheating medium are heated.
 9. The process according to claim 1, whereinthe chemical reaction is carried out in a flow-through reactor that isat least partially filled with the solid heating medium and therebypossesses at least one heating zone that can be heated byelectromagnetic induction, wherein the reaction medium flows through theflow-through reactor and wherein the inductor is located outside thereactor.
 10. The process according to claim 9, wherein the reactionmedium flows once or a plurality of times through the flow-thoughreactor with a speed such that the total contact time of the reactionmedium with the heating medium is in the range of one second to 2 hours.11. The process according to claim 1, wherein the reactor is configuredas a pressure reactor and the chemical reaction is carried out at apressure greater than atmospheric pressure, preferably under at least1.5 bar.
 12. The process according to claim 1, wherein the heatingmedium is ferromagnetic and exhibits a Curie temperature in the range of40 to 250° C., and is selected such that the Curie Temperature does notdiffer by more than 20 ° C. from the selected reaction temperature. 13.The process according to claim 1, wherein a chemical bond is formedbetween two carbon atoms or between a carbon atom and an atom X in thechemical reaction, wherein X is selected from: H, B, O, N, S, P, Si, Ge,Sn, Pb, As, Sb, Bi and halogen.